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The pathogenic aβ43 is enriched in familial and sporadic Alzheimer disease.

Sandebring A, Welander H, Winblad B, Graff C, Tjernberg LO - PLoS ONE (2013)

Bottom Line: Levels of Aβ43, as well as Aβ40 and Aβ42, were quantified using ELISA.We compared quantitative data showing Aβ levels in occipital and frontal cortex from sporadic (SAD) and familial (FAD) AD cases, as well as non-demented (ND) controls.Results showed Aβ43 present in each fraction from the SAD and FAD cases, while its level was lower than the detection limit in the majority of the ND-cases.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, KI-Alzheimer's Disease Research center (KI-ADRC), Huddinge, Sweden.

ABSTRACT
The amyloid-cascade hypothesis posits that the role of amyloid β-peptide (Aβ) in Alzheimer disease (AD) involves polymerization into structures that eventually are deposited as amyloid plaques. During this process, neurotoxic oligomers are formed that induce synaptic loss and neuronal death. Several different isoforms of Aβ are produced, of which the 40 and 42 residue variants (Aβ40 and Aβ42) are the most common. Aβ42 has a strong tendency to form neurotoxic aggregates and is involved in AD pathogenesis. Longer Aβ isoforms, like the less studied Aβ43, are gaining attention for their higher propensity to aggregate into neurotoxic oligomers. To further investigate Aβ43 in AD, we conducted a quantitative study on Aβ43 levels in human brain. We homogenized human brain tissue and prepared fractions of various solubility; tris buffered saline (TBS), sodium dodecyl sulfate (SDS) and formic acid (FA). Levels of Aβ43, as well as Aβ40 and Aβ42, were quantified using ELISA. We compared quantitative data showing Aβ levels in occipital and frontal cortex from sporadic (SAD) and familial (FAD) AD cases, as well as non-demented (ND) controls. Results showed Aβ43 present in each fraction from the SAD and FAD cases, while its level was lower than the detection limit in the majority of the ND-cases. Aβ42 and Aβ43 were enriched in the less soluble fractions (SDS and FA) of SAD and FAD cases in both occipital and frontal cortex. Thus, although the total levels of Aβ43 in human brain are low compared to Aβ40 and Aβ42, we suggest that Aβ43 could initiate the formation of oligomers and amyloid plaques and thereby be crucial to AD pathogenesis.

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Related in: MedlinePlus

Study Subject Data.ND = non-demented; SAD = sporadic Alzheimer disease; FAD = familial Alzheimer disease; y = years; M = male; F = female; PMI = postmortem interval; h = hours; Clinic = clinical neurological diagnosis; dem = demented; APPswe = Swedish mutation in APP; PS1I143T = I143T mutation in PSEN1; NP = neuropathological diagnosis; NH = neurologically healthy; pro AD = probable AD; pos AD = possible AD; def AD = definite AD. NH* = case excluded from grouped analysis.
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pone-0055847-g001: Study Subject Data.ND = non-demented; SAD = sporadic Alzheimer disease; FAD = familial Alzheimer disease; y = years; M = male; F = female; PMI = postmortem interval; h = hours; Clinic = clinical neurological diagnosis; dem = demented; APPswe = Swedish mutation in APP; PS1I143T = I143T mutation in PSEN1; NP = neuropathological diagnosis; NH = neurologically healthy; pro AD = probable AD; pos AD = possible AD; def AD = definite AD. NH* = case excluded from grouped analysis.

Mentions: Human brain specimens were obtained from the Brain bank at Karolinska Institutet (2011/962-31/1). Samples from six cognitively healthy non-demented (ND) individuals (three males and three females) were included. Nine cases with clinical dementia were included, six that had subsequently been neuropathologically diagnosed with SAD and three FAD cases (one APP Swedish mutation carrier and two PSEN1 Ile143Thr mutation carriers). The postmortem intervals (PMI), neuropathological (NP) and clinical diagnose, age and gender distribution by diagnostic group, including ND, SAD and FAD are presented in Figure 1.


The pathogenic aβ43 is enriched in familial and sporadic Alzheimer disease.

Sandebring A, Welander H, Winblad B, Graff C, Tjernberg LO - PLoS ONE (2013)

Study Subject Data.ND = non-demented; SAD = sporadic Alzheimer disease; FAD = familial Alzheimer disease; y = years; M = male; F = female; PMI = postmortem interval; h = hours; Clinic = clinical neurological diagnosis; dem = demented; APPswe = Swedish mutation in APP; PS1I143T = I143T mutation in PSEN1; NP = neuropathological diagnosis; NH = neurologically healthy; pro AD = probable AD; pos AD = possible AD; def AD = definite AD. NH* = case excluded from grouped analysis.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3569467&req=5

pone-0055847-g001: Study Subject Data.ND = non-demented; SAD = sporadic Alzheimer disease; FAD = familial Alzheimer disease; y = years; M = male; F = female; PMI = postmortem interval; h = hours; Clinic = clinical neurological diagnosis; dem = demented; APPswe = Swedish mutation in APP; PS1I143T = I143T mutation in PSEN1; NP = neuropathological diagnosis; NH = neurologically healthy; pro AD = probable AD; pos AD = possible AD; def AD = definite AD. NH* = case excluded from grouped analysis.
Mentions: Human brain specimens were obtained from the Brain bank at Karolinska Institutet (2011/962-31/1). Samples from six cognitively healthy non-demented (ND) individuals (three males and three females) were included. Nine cases with clinical dementia were included, six that had subsequently been neuropathologically diagnosed with SAD and three FAD cases (one APP Swedish mutation carrier and two PSEN1 Ile143Thr mutation carriers). The postmortem intervals (PMI), neuropathological (NP) and clinical diagnose, age and gender distribution by diagnostic group, including ND, SAD and FAD are presented in Figure 1.

Bottom Line: Levels of Aβ43, as well as Aβ40 and Aβ42, were quantified using ELISA.We compared quantitative data showing Aβ levels in occipital and frontal cortex from sporadic (SAD) and familial (FAD) AD cases, as well as non-demented (ND) controls.Results showed Aβ43 present in each fraction from the SAD and FAD cases, while its level was lower than the detection limit in the majority of the ND-cases.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, KI-Alzheimer's Disease Research center (KI-ADRC), Huddinge, Sweden.

ABSTRACT
The amyloid-cascade hypothesis posits that the role of amyloid β-peptide (Aβ) in Alzheimer disease (AD) involves polymerization into structures that eventually are deposited as amyloid plaques. During this process, neurotoxic oligomers are formed that induce synaptic loss and neuronal death. Several different isoforms of Aβ are produced, of which the 40 and 42 residue variants (Aβ40 and Aβ42) are the most common. Aβ42 has a strong tendency to form neurotoxic aggregates and is involved in AD pathogenesis. Longer Aβ isoforms, like the less studied Aβ43, are gaining attention for their higher propensity to aggregate into neurotoxic oligomers. To further investigate Aβ43 in AD, we conducted a quantitative study on Aβ43 levels in human brain. We homogenized human brain tissue and prepared fractions of various solubility; tris buffered saline (TBS), sodium dodecyl sulfate (SDS) and formic acid (FA). Levels of Aβ43, as well as Aβ40 and Aβ42, were quantified using ELISA. We compared quantitative data showing Aβ levels in occipital and frontal cortex from sporadic (SAD) and familial (FAD) AD cases, as well as non-demented (ND) controls. Results showed Aβ43 present in each fraction from the SAD and FAD cases, while its level was lower than the detection limit in the majority of the ND-cases. Aβ42 and Aβ43 were enriched in the less soluble fractions (SDS and FA) of SAD and FAD cases in both occipital and frontal cortex. Thus, although the total levels of Aβ43 in human brain are low compared to Aβ40 and Aβ42, we suggest that Aβ43 could initiate the formation of oligomers and amyloid plaques and thereby be crucial to AD pathogenesis.

Show MeSH
Related in: MedlinePlus